What Is an Endometrial Receptivity Analysis (ERA)?
To understand what an endometrial receptivity analysis (ERA) is, first you have to know what the endometrium is. The endometrium is the lining of the uterus. It changes during pregnancy and during the menstrual cycle to provide an ideal environment for the implantation of a fertilized egg and the growth of the placenta. Endometrial receptivity is the ability of the endometrium to provide this ideal environment for the growing embryo. An ERA is a test that measures certain characteristics of the endometrium to determine the best time for the implantation of an embryo during IVF.
How Does an ERA Work?
Many markers of receptivity have been studied, including endometrial thickness and pattern, wave-like activity, and the presence of various molecules or expressions of various genes. Techniques used for ERAs include ultrasound, hysteroscopy, and fluid samples. The most common test is an endometrial biopsy. The patient undergoes a standard round of IVF hormone treatments. At the point in the cycle where an embryo would be transferred, the ERA is performed instead. The endometrial lining is scratched to provide a biopsy sample, which is sent to a lab for genetic sequencing. The cost can be up to $1,000, and the results take a few weeks to come back. Over 200 genes are tested in the genetic array, in a search for molecular signals that indicate that the uterus is ready for embryo implantation. Based on the genes expressed, the endometrium at the time of the sample is classified as non-receptive, pre-receptive, receptive, or post-receptive. If the patient’s endometrium is not receptive, the hormone regimen is adjusted to bring the patient into the receptive phase, explains Nicole Doyle, MD, PhD, FACOG, a fertility specialist at Shady Grove Fertility. Some sources say that ERA promises to narrow down the ideal implantation window to a six-hour period, and others that the window of implantation is 30 to 36 hours.
What Are the Benefits of the ERA Test?
Proponents of endometrial receptivity analysis say that without the ERA test, 30% of IVF cycles fail because the embryo transfer is done outside of the window of implantation. A total of 238 genes express differently depending on the stage of the fertility cycle, allowing doctors to find the ideal embryo implantation time. There’s data that indicates that the biopsy process itself may affect the patient’s fertility cycle. “[The endometrial scratch can] result in a remodeling of the uterine lining, and that remodeling creates an inflammation reaction that can potentially increase pregnancy results in a subsequent cycle,” says Dr. Doyle. But, she points out, there are also studies that say this is not the case.
What Are the Drawbacks of the ERA Test?
There are a few downsides to performing an ERA. “It takes several weeks to do, it is invasive, and it’s painful,” says Dr. Doyle. There’s also no indication that an ERA is actually useful to IVF patients. Much of the research is sponsored by testing companies, resulting in conflicts of interest. Additionally, looking at the endometrial receptivity field as a whole is inconclusive because of the number of variables. Testing can occur at many different times during the fertility cycle, while using embryos of different quality, implanting embryos at different times, and working with different equipment. Some studies have poor data due to bias, inconsistency, and imprecision. A patient’s window of implantation can also change from cycle to cycle. “There is some inter-cycle variability and there has been way too little research,” says Lien Dhaenens, OB/GYN, an endometrial researcher at University Hospital in Ghent, Belgium. “We don’t even know how close in vitro models are to the real thing.”
Should You Get an ERA?
ERA is a relatively new technique that has not been extensively tested, but it has been popularized and commercialized. This makes it controversial, says Dr. Dhaenens. “[Endometrial receptivity] is more of a concept,” she says. “It’s not a clear diagnosis. So it’s a bit short-sighted to think that you can actually test for it.” Dr. Doyle and her colleagues performed a randomized clinical trial in which almost 800 good-prognosis IVF patients were divided into two groups: one with embryos transferred when indicated by ERA, and one with embryos transferred according to the standard schedule. The transfer was considered successful if it resulted in a live birth. The result? There was no difference in the live birth rate between the ERA patients and the non-ERA patients. Some patients may request an ERA, especially those who struggle to become pregnant over several IVF cycles. “Recurrent implantation failure might be ascribable to an endometrial factor in up to 25% of the cases,” says Dr. Doyle. “If receptivity status varies, maybe we should individualize these transfers.” She pointed out that her study did not include patients with recurrent implantation failure, uterine problems, poor quality embryos, or ages younger than 30 or older than 40. Dr. Doyle says that she gives her patients all of the data for them to make informed decisions. “We as a practice have a dedicated research division and use our own resources to answer questions important to our patients to validate the diagnostics that are offered to them appropriately,” she says. Part of that information is that there’s not really an accepted definition for recurrent implantation failure. A patient with three consecutive euploid embryo transfers has a success rate of 92%. Of the remaining patients, about half are completely non-receptive, and the rest may be able to benefit from an ERA test. “That is a very small fraction of our IVF population,” she says. Ultimately, it’s the patient’s choice, based on their research and the counsel of their physician.
A Word From Verywell
For patients who are concerned about recurrent implantation failure, an ERA might be the next logical step. However, it might not be the right test for every IVF patient. “[ERA is] going to be reserved for patients who actually need it, which would be those that are having recurrent implantation failure, or they have conditions that cause inflammation, like endometriosis,” says Anthony Imudia, MD, a fertility specialist at Shady Grove Fertility. Endometrial receptivity is a promising field, says Dr. Dhaenens, but there’s still a lot of research to be done. “Implantation is too much of a black box. You can’t enter it. Human reproduction isn’t as efficient as we want it to be, and failure is definitely part of it. And there are no guarantees.” Talk to your OB/GYN or healthcare provider about whether or not an ERA makes sense for you.
